What laboratory tests are recommended for a patient presenting with headache and fatigue?

Laboratory Testing for Headache and Fatigue

For patients presenting with headache and fatigue, obtain a comprehensive metabolic panel, complete blood count, thyroid function tests (TSH and free T4), morning cortisol and ACTH levels, inflammatory markers (ESR, CRP), and consider screening for anemia with iron studies. 1

Core Laboratory Panel

The initial laboratory workup should include:

• Complete blood count (CBC) with differential to assess for anemia, infection, or hematologic disorders 2, 1
• Serum electrolytes including calcium and magnesium to identify imbalances that can cause both symptoms 2, 1
• Blood urea nitrogen (BUN) and serum creatinine to evaluate kidney function 2, 1
• Fasting blood glucose or HbA1c to screen for diabetes mellitus 2, 1
• Liver function tests to evaluate hepatic disorders 2, 1
• Thyroid-stimulating hormone (TSH) and free T4 to screen for thyroid dysfunction, as hypothyroidism commonly presents with both headache and fatigue 2, 1
• Urinalysis to screen for renal disease or infection 2, 1

Extended Evaluation for Moderate to Severe Symptoms

When symptoms are moderate to severe (fatigue score ≥4 on a 0-10 scale), expand the workup to include:

• Morning cortisol and ACTH levels (preferably around 8 AM) to evaluate for adrenal insufficiency, which presents with both headache and fatigue 2
• C-reactive protein (CRP) to evaluate for inflammatory conditions 1
• Serum ferritin and transferrin saturation to assess iron status, as iron deficiency causes fatigue 1
• Vitamin B12 and folate levels to identify deficiencies that contribute to fatigue 1

Critical Diagnostic Considerations

Hypophysitis Screening (If Applicable Clinical Context)

If the patient has risk factors or concerning features, consider pituitary evaluation including:

• TSH and free T4 to detect central hypothyroidism (low TSH with low free T4) 2
• Morning ACTH and cortisol or cosyntropin stimulation test for central adrenal insufficiency 2
• Gonadal hormones (testosterone in men, estradiol in women) and FSH/LH if panhypopituitarism suspected 2

This is particularly important as headache occurs in 85% and fatigue in 66% of hypophysitis cases 2

Thyroid Dysfunction Assessment

Thyroid testing is essential because:

• Hypothyroidism presents with fatigue, and thyroid dysfunction occurs in 6-20% of certain patient populations 2
• If TSH is elevated with low free T4, add thyroid peroxidase (TPO) antibody testing 2
• If TSH is low/normal with elevated free T4 or T3, consider thyrotoxicosis and may need additional testing 2

Additional Testing Based on Clinical Suspicion

• Lipid profile to assess cardiovascular risk factors 2, 1
• Reticulocyte count if anemia is present to evaluate bone marrow response 1
• Haptoglobin, LDH, and bilirubin if hemolysis is suspected 1

Important Clinical Pitfalls

Avoid these common errors:

• Do not overlook central causes of hypothyroidism—a low TSH does not always mean normal thyroid function if free T4 is also low 2
• Always start corticosteroid replacement before thyroid hormone replacement if both deficiencies are present to avoid precipitating adrenal crisis 2
• Laboratory abnormalities affect management in only about 5% of fatigue cases, but are essential to rule out treatable causes 1
• Consider that fatigue and headache commonly coexist with depression and anxiety, which should be screened for clinically 2

Timing and Follow-up

• Repeat thyroid testing before each treatment cycle if monitoring is indicated, along with metabolic panel for glycemic trends 2
• Re-evaluate fatigue severity after addressing any treatable contributing factors identified 2, 1
• Consider specialized testing or consultation if initial workup is unrevealing but symptoms persist 1